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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2013

Open Access 01-12-2013 | Research article

Low dose native type II collagen prevents pain in a rat osteoarthritis model

Authors: Lorenzo Di Cesare Mannelli, Laura Micheli, Matteo Zanardelli, Carla Ghelardini

Published in: BMC Musculoskeletal Disorders | Issue 1/2013

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Abstract

Background

Osteoarthritis is the most widespread joint-affecting disease. Patients with osteoarthritis experience pain and impaired mobility resulting in marked reduction of quality of life. A progressive cartilage loss is responsible of an evolving disease difficult to treat. The characteristic of chronicity determines the need of new active disease modifying drugs. Aim of the present research is to evaluate the role of low doses of native type II collagen in the rat model of osteoarthritis induced by sodium monoiodoacetate (MIA).

Methods

1, 3 and 10 mg kg-1 porcine native type II collagen were daily per os administered for 13 days starting from the day of MIA intra-articular injection.

Results

On day 14, collagen-treated rats showed a significant prevention of pain threshold alterations induced by MIA. Evaluation were performed on paws using mechanical noxious (Paw pressure test) or non-noxious (Electronic Von Frey test) stimuli, and a decrease of articular pain was directly measured on the damaged joint (PAM test). The efficacy of collagen in reducing pain was as higher as the dose was lowered. Moreover, a reduced postural unbalance, measured as hind limb weight bearing alterations (Incapacitance test), and a general improvement of motor activity (Animex test) were observed. Finally, the decrease of plasma and urine levels of CTX-II (Cross Linked C-Telopeptide of Type II Collagen), a biomarker of cartilage degradation, suggests a collagen-dependent decrease of structural joint damage.

Conclusions

These results describe the preclinical efficacy of low dosages of native type II collagen as pain reliever by a mechanism that involves a protective effect on cartilage.
Appendix
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Literature
1.
Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF: Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000, 133: 635-646. 10.7326/0003-4819-133-8-200010170-00016.CrossRefPubMed
2.
Mow VC, Setton LA, Fuilak F, Ratcliffe A: Mechanical factors in articular cartilage and their role in osteoarthritis. Osteoarthritic disorders. Edited by: Kuettner KE, Goldberg VM. 1995, Rosemont (IL): American Academy of Orthopaedic Surgeons, 147-172.
3.
ANON: Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arth Rheum. 2000, 43: 1905-1915.CrossRef
4.
Eyre D: Articular cartilage and changes in Arthritis: Collagen of articular cartilage. Arthritis Res. 2002, 4: 30-35.CrossRefPubMed
5.
Van Vijven JPJ, Luijsterburg PAJ, Verhagen AP, Van Osch GJVM, Kloppenburg M, Bierma-Zeinstra SMA: Symptomatic and chondroprotective treatment with collagen derivatives in osteoarthritis: a systematic review. Osteoarthr Cartil. 2012, 20: 809-821. 10.1016/j.joca.2012.04.008.CrossRefPubMed
6.
Oesser S, Adam M, Babel W, Seifert J: Oral administration of (14)C labelled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). J Nutr. 1999, 129: 1891-1895.PubMed
7.
Oesser S, Seifert J: Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen. Cell Tissue Res. 2003, 311: 393-399.PubMed
8.
Schunck M, Schulze CH, Oesser S: Disparate efficacy of collagen hydrolysate and glucosamine on the extracellular matrix metabolism of articular chondrocytes. Osteoarthritis Cartilage. 2006, 14: S114-CrossRef
9.
Koyama Y, Hirota AH, Irie S: Ingestion of gelatin has differential effect on bone mineral density and body weight in protein undernutrition. J Nutr Sci Vitaminol. 2001, 47: 84-86. 10.3177/jnsv.47.84.CrossRefPubMed
10.
Nomura Y, Oohashi K, Watanabe M, Kasugai S: Increase in bone mineral density through oral administration of shark gelatin to ovariectomized rats. Nutrition. 2005, 21: 1120-1126. 10.1016/j.nut.2005.03.007.CrossRefPubMed
11.
Faria M, Da Costa EL, Gontijo JAR, Netto FM: Evaluation of the hypotensive potential of bovine and porcine collagen hydrolysates. J Med Food. 2008, 11: 560-567. 10.1089/jmf.2007.0573.CrossRefPubMed
12.
Zhang Y, Koguchi T, Simizu M, Ohmori T, Takahata Y, Morimatsu F: Chicken collagen hydrolysate protects rats from hypertension and cardiovascular damage. J Med Food. 2010, 13: 399-405. 10.1089/jmf.2009.1246.CrossRefPubMed
13.
McCarthy S, Carpenter MR, Barrell MM, Morrissey DE, Jacobson E, Kline G:The effectiveness of gelatine supplementation treatment in individuals with symptoms of mild osteoarthritis. A randomized, doubleblind, placebo-controlled study.US Family Practice News; American Academy of Family Physicians. 2000, Dallas (TX): Annual Assembly,
14.
Moskowitz RW: Role of collagen hydrolysate in bone and joint disease. Semin Arthritis Rheum. 2000, 30: 87-99. 10.1053/sarh.2000.9622.CrossRefPubMed
15.
McAlindon TE, Nuite M, Krishnan N, Ruthazer R, Price LL, Burstein D, Griffith J, Flechsenhar K: Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. Osteoarthr Cartil. 2011, 19: 399-405. 10.1016/j.joca.2011.01.001.CrossRefPubMed
16.
Wei W, Zhang LL, Xu JH, Xiao F, Bao CD, Ni LQ, Li XF, Wu YQ, Sun LY, Zhang RH, Sun BL, Xu SQ, Liu S, Zhang W, Shen J, Liu HX, Wang RC: A multicenter, double blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Res Ther. 2009, 11: R180-10.1186/ar2870.CrossRefPubMedPubMedCentral
17.
Park KS, Park MJ, Cho ML, Kwok SK, Ju JH, Ko HJ, Park SH, Kim HY: Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheumatoid arthritis. Mod Rheumatol. 2009, 19: 581-589. 10.1007/s10165-009-0210-0.CrossRefPubMed
18.
Mowat AM: Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol. 2003, 3: 331-341. 10.1038/nri1057.CrossRefPubMed
19.
20.
Ilan Y: Oral tolerance: Can we make it work?. Hum Immunol. 2009, 70: 768-776. 10.1016/j.humimm.2009.06.018.CrossRefPubMed
21.
Crowley DC, Lau FC, Sharma P, Evans M, Guthrie N, Bagchi M, Bagchi D, Dey DK, Raychaudhuri SP: Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci. 2009, 6: 312-321.CrossRefPubMedPubMedCentral
22.
Guingamp C, Gegout-Pottie P, Philippe L, Terlain B, Netter P, Gillet P: Mono iodoacetate-induced experimental osteoarthritis: a dose-response study of loss of mobility, morphology, and biochemistry. Arthritis Rheum. 1997, 40: 1670-1679. 10.1002/art.1780400917.CrossRefPubMed
23.
Pomonis JD, Boulet JM, Gottshall SL, Phillips S, Sellers R, Bunton T, Walker K: Development and pharmacological characterization of a rat model of osteoarthritis pain. Pain. 2005, 114: 339-346. 10.1016/j.pain.2004.11.008.CrossRefPubMed
24.
Leighton GE, Rodriguez RE, Hill RG, Hughes J: k-opioid agonist produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat. Br J Pharmacol. 1988, 93: 553-560. 10.1111/j.1476-5381.1988.tb10310.x.CrossRefPubMedPubMedCentral
25.
Sakurai M, Egashira N, Kawashiri T, Yano T, Ikesue H, Oishi R: Oxaliplatin-induced neuropathy in the rat: involvement of oxalate in cold hyperalgesia but not mechanical allodynia. Pain. 2009, 147: 165-174. 10.1016/j.pain.2009.09.003.CrossRefPubMed
26.
Bove SE, Calcaterra SL, Brooker RM, Huber CM, Guzman RE: Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthr Cartil. 2003, 11: 821-830. 10.1016/S1063-4584(03)00163-8.CrossRefPubMed
27.
Oestergaard S, Chouinard L, Doyle N, Karsdal MA, Smith SY, Qvist P, Tankó LB: The utility of measuring C-terminal telopeptides of collagen type II (CTX-II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases. Osteoarthritis Cartilage. 2006, 14: 670-679. 10.1016/j.joca.2006.01.004.CrossRefPubMed
28.
Driban JB, Barr AE, Amin M, Sitler MR, Barbe MF: Joint Inflammation and Early Degeneration Induced by High-Force Reaching Are Attenuated by Ibuprofen in an Animal Model ofWork-RelatedMusculoskeletal Disorder. J Biomed Biotechnol. 2011, 2011: 691412-10.1155/2011/691412.CrossRefPubMedPubMedCentral
29.
Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Zhang X, Tajino J, Kuroki H: Effects of Exercise Level on Biomarkers in a Rat Knee Model of Osteoarthritis. J Orthop Res. 2013, 31: 1026-1031. 10.1002/jor.22332.CrossRefPubMed
30.
31.
Mathers CD, Vos ET, Stevenson CE, Begg SJ: The Australian burden of disease study: measuring the loss of health from diseases, injuries and risk factors. Med J Aust. 2000, 172: 592-596.PubMed
32.
Piscitelli P, Iolascon G, Di Tanna G, Bizzi E, Chitano G, Argentiero A, Neglia C, Giolli L, Distante A, Gimigliano R, Brandi ML, Migliore A: Socioeconomic burden of total joint arthroplasty for symptomatic hip and knee osteoarthritis in the Italian population: a 5-year analysis based on hospitalization records. Arthritis Care Res (Hoboken). 2012, 64: 1320-1327. 10.1002/acr.21706.CrossRef
33.
Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F: National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008, 58: 26-35. 10.1002/art.23176.CrossRefPubMed
34.
Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH: National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008, 58: 15-25. 10.1002/art.23177.CrossRefPubMed
35.
36.
World Health Organization: The burden of musculoskeletal conditions at the start of the new millennium. 2003, Geneva: WHO technical report series 919
37.
38.
Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P: OARSI recommendations for the management of hip and knee osteoarthritis, Part II. OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008, 16: 137-62. 10.1016/j.joca.2007.12.013.CrossRefPubMed
39.
Di Cesare Mannelli L, Bani D, Bencini A, Brandi ML, Calosi L, Cantore M, Carossino AM, Ghelardini C, Valtancoli B, Failli P: Therapeutic Effects of the Superoxide Dismutase Mimetic Compound Me2DO2A on Experimental Articular Pain in Rats. Mediat Inflamm. 2013, 10.1155/2013/905360.
40.
Kobayashi K, Imaizumi R, Sumichika H, Tanaka H, Goda M, Fukunari A, Komatsu H: Sodium iodoacetate-induced experimental osteoarthritis and associated pain model in rats. J Vet Med Sci. 2003, 65: 1195-1199. 10.1292/jvms.65.1195.CrossRefPubMed
41.
van der Kraan PM, Vitters EL, van de Putte LB, van den Berg WB: Development of osteoarthritic lesions in mice by “metabolic” and “mechanical” alterations in the knee joints. Am J Pathol. 1989, 135: 1001-1014.PubMedPubMedCentral
42.
Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K: Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis. Toxicol Pathol. 2003, 31: 619-624.CrossRefPubMed
43.
Izumi M, Ikeuchi M, Ji Q, Tani T: Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis. J Biomed Sci. 2012, 19: 77-10.1186/1423-0127-19-77.CrossRefPubMedPubMedCentral
44.
Rousseau JC, Delmas PD: Biological markers in osteoarthritis. Nat Clin Pract Rheumatol. 2007, 3: 346-56. 10.1038/ncprheum0508.CrossRefPubMed
45.
De Ceuninck F, Sabatini M, Pastoureau P: Recent progress toward biomarker identification in osteoarthritis. Drug Discovery Today. 2011, 16: 443-449. 10.1016/j.drudis.2011.01.004.CrossRefPubMed
46.
De Ceuninck F, Sabatini M, Renoux V, De Nanteuil G, Pastoureau P: Urinary collagen type II C-telopeptide fragments are sensitive markers of matrix metalloproteinase-dependent cartilage degradation in rat adjuvant-induced arthritis. J Rheumatol. 2003, 130: 1561-1564.
47.
Sowers MF, Karvonen-Gutierrez CA, Yosef M, Jannausch M, Jiang Y, Garnero P, Jacobson J: Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women. Osteoarthritis Cartilage. 2009, 17: 1609-1614. 10.1016/j.joca.2009.06.001.CrossRefPubMedPubMedCentral
48.
Sharif F, Kirwan J, Charni N, Sandell LJ, Whittles C, Garnero P: A 5-yr longitudinal study of type IIA collagen synthesis and total type II collagen degradation in patients with knee osteoarthritis – association with disease progression. Rheumatology. 2007, 46: 938-943. 10.1093/rheumatology/kel409.CrossRefPubMed
49.
Chen FH, Rousche KT, Tuan RS: Technology Insight: adult stem cells in cartilage regeneration and tissue engineering. Nat Clin Pract Rheumatol. 2006, 2: 373-382. 10.1038/ncprheum0216.CrossRefPubMed
50.
Nagler-Anderson C, Bober LA, Robinson ME, Siskind GW, Thorbecke GJ: Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci U S A. 1986, 83: 7443-7446. 10.1073/pnas.83.19.7443.CrossRefPubMedPubMedCentral
51.
Castro-Sánchez P, Martín-Villa JM: Gut immune system and oral tolerance. Br J Nutr. 2013, 109 (Suppl 2): S3-S11.CrossRefPubMed
52.
Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HL: Effects of oral administration of type II collagen on rheumatoid arthritis. Science. 1993, 261: 1727-1730. 10.1126/science.8378772.CrossRefPubMed
53.
McDole JR, Wheeler LW, McDonald KG, Wang B, Konjufca V, Knoop KA, Newberry RD, Miller MJ: Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature. 2012, 483: 345-349. 10.1038/nature10863.CrossRefPubMedPubMedCentral
Metadata
Title
Low dose native type II collagen prevents pain in a rat osteoarthritis model
Authors
Lorenzo Di Cesare Mannelli
Laura Micheli
Matteo Zanardelli
Carla Ghelardini
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2013
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-14-228

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